Associations between CCL21 gene polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis

Rheumatoid arthritis (RA) is a chronic systemic disorder characterized by the development through angiogenesis, which is dependent on endothelial cell activation, migration and proliferation and CCL21 plays an important role in this pathology. Currently, CCL21 gene polymorphism studies on rheumatoid arthritis are scarce and the results are diverse. This meta-analysis was performed to determine if CCL21 gene polymorphisms correlate with the risk of developing RA. Association reports for the relationship between CCL21 polymorphisms and RA were identified from PubMed, Cochrane Library, Embase, SCIELO, CNKI and Wanfang databases on March 22, 2017. The odds ratio (OR) and 95% confidence interval (CI) were applied to assess the relationship strength. Publication bias was conducted with Begg's funnel plot and Egger's regression test to measure the robustness of our findings. Sensitivity and cumulative analyses were used to assess the overall robustness of the study's results. Four relevant case-control cohort studies and three GWAS studies with CCL21rs2812378G>A gene polymorphisms and rheumatoid arthritis involving 9963 RA cases and 7976 controls were identified. Significant associations between the CCL21 rs2812378G>A polymorphism and RA risk were observed in the co-dominant model, dominant model and heterozygous model (A vs G: OR = 1.08, 95% CI = 1.03-1.14, p < 0.01, I ² = 0.0%; AA + AG vs GG: OR = 1.15, 95% CI = 1.05-1.28, p < 0.01, I ² = 0.0%; AG vs GG: OR = 1.18, 95% CI = 1.08-1.30, p < 0.01, I ² = 3.8%) in the total population, as well as in subgroup Caucasian population. The combined analysis revealed a significantly increased risk of rheumatoid arthritis in the co-dominant model, dominant model and heterozygous model in overall population and subgroup Caucasian population.